We are studying the ways in which nerves and muscles work together to determine and maintain muscle form and function by focusing on how acetylcholinesterase (AChE), an important enzyme found at the neuromuscular junction, is regulated in the chicken and, secondarily, how its activity and its localization become defective in birds with an inherited muscular dystrophy. We use cell cultures to study how newly synthesized AChE moves, binds, assembles and is released from the muscle cells. Denervation studies show that neural activity localizes AChE at the neuromuscular junction. Limb bud transplants between normal and dystrophic 3 1/2day embryos prove that after this age that the defect in AChE regulation of dystrophic chickens resides in their muscles and not in their nerves. Electrical stimulation of cultures and denervated muscles show that activity reversibly decreases AChE. We find that the increase of AChE in cultured muscle with acetylcholine analogs is not controlled by DNA mediated RNA synthesis but it is abolished by drugs that block neuromuscle transmission. Similar AChE regulations happen in nerve and in muscle cultures. This year we will use electron microscopy to examine the movement of AChE through and out of muscle and nerve cells and follow up our findings that AChE is high throughout the length of denervated fibers but is high only around the neuromuscular junction of dystrophic fibers. BIBLIOGRAPHIC REFERENCES: Linkhart, T.A., Yee, G.W., Nieberg, P.A. and Wilson, B.W. 1976 Myogenic defect in muscular dystrophy of the chicken. Devel. Biology. Patterson, G.T. and Wilson, B.W. 1976 Distribution of extrajunctional acetylcholinesterase in muscle: normal and dystrophic chickens. Exp. Neurol.